Amphotericin B: A Potential Anecdote For the Hair of the Dog That Bit You


BY MICHAEL HERRON | UTS WRITER | SQ 2017-2018


 

I N T R O D U C T I O N

 

Alcoholism presents itself as the pink elephant in the room, a global conundrum that persists despite researchers’ best attempts to resolve such legal substance abuse. This disease is noted by excessive alcoholic intake, which is classified as fifteen drinks or more per week for men and eight or more drinks per week for women. It  is ranked as one of the leading causes of mortality worldwide, with addiction being most prevalent amongst ages 15-74.

This disease is commonly associated with a myriad of related health issues, such as cirrhosis. Cirrhosis is the irreversible scarring of the liver caused by a buildup of fibrosis scar tissue caused by inflammation from excessive alcohol intake. There are two main stages of alcohol- induced cirrhosis: compensated cirrhosis and decompensated cirrhosis. Compensated cirrhosis patients typically show no signs of disease, although inflammation of the liver via injury is well underway that leads to increased white blood cell count and activation of cell-signaling pathways.

Decompensated cirrhosis, in contrast, leads to patients showing notably stark symptoms of excessive alcohol use, such as swelling of the abdomen and feet known as ascites.This stage, if left untreated, will further progress into alcoholic end- stage liver disease-which leads to the failure of the liver and typically results in death.

There are limited options currently available to alleviate the irreversible effects of chronic alcoholism, including organ transplants, dialysis treatments to filter bodily waste, diuretics to reduce water retention, and pain relievers. The search for further solutions lies in the hands of not only researchers, but also members in various fields such as healthcare and legislation. Despite community efforts and city council proposals, alcoholism continues to present a nine percent increase within California’s local communities, such as San Diego. San Diego County Medical Examiner’s Office, for example, revealed alcohol- related deaths as the second- highest cause of death in 2015.

Currently, there is no cure for alcohol addiction nor cirrhosis, with the two main options being rehabilitation or minimizing the symptoms to limit liver injury progression. One of the main areas of research being studied for reducing the effects of cirrhosis is inflammatory pathways. Alcohol is a known factor in activation inflammatory pathways as the body responds to liver cells’ injury to prevent further damage from its ingestion. The onset of inflammation within the organ, alongside the systemic effects that occur due to cell signaling, leads to a circuit of a downward spiral for the alcoholic’s state of health. The fields of cellular and molecular biology has led to findings that may be useful for alcoholism inflammatory treatment in hopes of lessening the severity of liver disease, such as current research conducted at UC San Diego.

 

R E S E A R C H

 

In 2017, UC San Diego’s School of Medicine’s Department of Gastroenterology  Dr. Bernd Schnabl’s research team examined the intestinal tract’s flouri of chronic alcoholics versus nonalcoholics to determine a correlation between fungal levels within patient’s microbiota gut community in regards to the onset of disease

Mice underwent chronic alcohol exposure and then were subjected to intestinal cultures to note of fungal populational levels . The results suggested that fungi thriving successfully within the lab mice’ intestines enduring chronic alcohol use had profound effects for liver disease progression. This included the mice showcasing symptoms of deterring cirrhosis through increase inflammation of the intestinal walls. The cirrhotic inflammation allowed the mice’ fungal cells to move across the weakened abdominal cavity lining and translocate within its surrounding organs. The placement of the fungal cells into organs that lacked recognition of the newly introduced fungi led to a subsequent inflammatory response by the mouse’s immune cells and thus triggered increased chronic inflammation associated with the mouse’s cirrhotic state.

The chronic alcoholic mice’s enzyme blood levels were then examined post-receival of an oral antifungal medication, amphotericin B, to counteract the effects of fungal β-Glucan cell wall movement into the intestinal cavity. This led to reduced levels of fungal cells found within the alcoholic mouse’s intestinal flora and thus lessened the severity of inflammation and fat buildup within the liver. The most prominent liver components studied, the enzyme alanine aminotransferase and its triglyceride levels, were strikingly reduced by 55% and 21 %, respectively. Key liver enzymes levels, such as alanine aminotransferase, tend to skyrocket in response to excessive alcohol consumption.

The reduction of important liver components like triglycerides that are useful in assessing the organ’s state of health indicate oral amphotericin B’s effect of reducing alcoholic inflammation of the liver. This showcased an immense success in the study of liver disease, with oral amphotericin B targeting solely intestinal fungal cells, leading to no known systemic side effects unlike its intravenous counterpart.

The influence of fungal growth upon the mouse’s response through increased chronic liver inflammatory pathway activation suggests that chronic inflammatory activation via alcoholism is linked to an altered fungal microbiota within the gut. This leads to the possibility of marketing oral amphotericin B for future control of cirrhosis treatment, as well as further studies of the role fungi play in heightening the onset of liver inflammation. Dr. Schnabl’s research team’s effort has projected a potential treatment plan for afflicted alcoholics of cirrhosis, a field of research that currently presents a bleak understanding in counteracting the effects of long-term alcohol abuse.

 

W O R K S   C I T E D

 

University of California – San Diego. “Intestinal fungi worsen alcoholic liver disease: Reducing intestinal fungi slowed disease progression in mice.” ScienceDaily. ScienceDaily, 23 May

Wagner, Dr. Glenn. “ County of San Diego Department of the Medical Examiner 2015 Annual Report”. Web. 7 July 2017.

 


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